College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Toxins (Basel). 2018 Jun 9;10(6):235. doi: 10.3390/toxins10060235.
Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli⁻germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli⁻germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli⁻germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.
微囊藻氨酸亮氨酸精氨酸（MC-LR）是一种由蓝藻产生的环状七肽，是一种强烈的生殖毒素。在大鼠支持细胞和中国仓鼠卵巢细胞中的研究表明，MC-LR 暴露后会产生典型的细胞凋亡。然而，对于如何预防 MC-LR 引起的生殖毒性知之甚少。本研究旨在探讨白藜芦醇（RES）对支持细胞-生殖细胞共培养物和大鼠睾丸的抗凋亡和保护作用的可能分子机制。结果表明，MC-LR 处理抑制了支持细胞-生殖细胞的增殖并诱导了细胞凋亡。此外，SIRT1 和 Bcl-2 受到抑制，而 p53 和 Ku70 乙酰化、Bax 表达和 cleaved caspase-3 被 MC-LR 上调。然而，RES 预处理改善了 MC-LR 诱导的细胞凋亡和 SIRT1 抑制，并下调了 MC-LR 诱导的 p53 和 Ku70 乙酰化、Bax 表达和 caspase-3 激活增加。此外，RES 逆转了 MC-LR 介导的 Ku70 与 Bax 结合减少。本研究表明，RES 的给药可以通过刺激 SIRT1/p53 途径、抑制 p53 和 Ku70 乙酰化以及增强 Ku70 与 Bax 的结合，改善 MC-LR 诱导的支持细胞-生殖细胞凋亡，并保护大鼠免受生殖毒性。
